Promoting psychological health in women with SCI: Development of an online self-esteem intervention.

Background: There are no known interventions addressing self-esteem in women following spinal cord injury (SCI).

Objectives: To test the feasibility of an online self-esteem intervention for women with disabilities, as modified for women with SCI.

Method: We conducted a randomized, controlled feasibility test of a self-esteem intervention (N = 21).

A pilot test of the GoWoman weight management intervention for women with mobility impairments in the online virtual world of Second Life.

Pilot test GoWoman, a small-group weight management intervention for mobility impaired women that was a disability- and gender-responsive adaptation of the Diabetes Prevention Program delivered in the online virtual world of Second Life. Objectives were to (1) examine pre-/post-intervention differences in weight, waist circumference, diet, physical activity, self-efficacy for diet and physical activity, nutrition knowledge and social support for weight management, (2) determine intervention feasibility (fidelity, attrition, engagement, acceptability). Single-group modified interrupted time series quasi-experimental design whereby participants served as their own controls.

Muscle Fatigue from the Perspective of a Single Crossbridge.

The repeated intense stimulation of skeletal muscle rapidly decreases its force- and motion-generating capacity. This type of fatigue can be temporally correlated with the accumulation of metabolic by-products, including phosphate (Pi) and protons (H). Experiments on skinned single muscle fibers demonstrate that elevated concentrations of these ions can reduce maximal isometric force, unloaded shortening velocity, and peak power, providing strong evidence for a causative role in the fatigue process.

An Internet-based virtual reality intervention for enhancing self-esteem in women with disabilities: Results of a feasibility study.

Purpose: To examine the feasibility of an online self-esteem enhancement group program for women with disabilities.

Method: A sample of 19 racially and ethnically diverse, community-living women with physical disabilities, 22 to 61 years old, participated in a 7-session interactive group intervention (extending Hughes et al., 2004) in the 3-D, immersive, virtual environment of SecondLife.

Hyperthermia: from diagnostic and treatments to new discoveries.

Hyperthermia is an important approach for the treatment of several diseases. Hyperthermia is also thought to induce hypertrophy of skeletal muscles in vitro and in vivo, and has been used as a therapeutic tool for millennia. In the first part of our work, we revise several relevant patents related to the utilization of hyperthermia for the treatment and diagnostic of human diseases.

Kruppel-like factor 15 regulates skeletal muscle lipid flux and exercise adaptation.

The ability of skeletal muscle to enhance lipid utilization during exercise is a form of metabolic plasticity essential for survival. Conversely, metabolic inflexibility in muscle can cause organ dysfunction and disease. Although the transcription factor Kruppel-like factor 15 (KLF15) is an important regulator of glucose and amino acid metabolism, its endogenous role in lipid homeostasis and muscle physiology is unknown.

Store-operated Ca(2+) entry (SOCE) contributes to normal skeletal muscle contractility in young but not in aged skeletal muscle.

Muscle atrophy alone is insufficient to explain the significant decline in contractile force of skeletal muscle during normal aging. One contributing factor to decreased contractile force in aging skeletal muscle could be compromised excitation-contraction (E-C) coupling, without sufficient available Ca(2+) to allow for repetitive muscle contractility, skeletal muscles naturally become weaker. Using biophysical approaches, we previously showed that store-operated Ca(2+) entry (SOCE) is compromised in aged skeletal muscle but not in young ones.

Muscle-specific inositide phosphatase (MIP/MTMR14) is reduced with age and its loss accelerates skeletal muscle aging process by altering calcium homeostasis.

We have recently reported that a novel muscle-specific inositide phosphatase (MIP/MTMR14) plays a critical role in [Ca2+]i homeostasis through dephosphorylation of sn-1-stearoyl-2-arachidonoyl phosphatidylinositol (3,5) bisphosphate (PI(3,5)P2). Loss of function mutations in MIP have been identified in human centronuclear myopathy. We developed a MIP knockout (MIPKO) animal model and found that MIPKO mice were more susceptible to exercise-induced muscle damage, a trademark of muscle functional changes in older subjects.

Temporal adaptive changes in contractility and fatigability of diaphragm muscles from streptozotocin-diabetic rats.

Diabetes is characterized by ventilatory depression due to decreased diaphragm (DPH) function. This study investigated the changes in contractile properties of rat DPH muscles over a time interval encompassing from 4 days to 14 weeks after the onset of streptozotocin-induced diabetes, with and without insulin treatment for 2 weeks. Maximum tetanic force in intact DPH muscle strips and recovery from fatiguing stimulation were measured.

Deficiency of MIP/MTMR14 phosphatase induces a muscle disorder by disrupting Ca(2+) homeostasis.

The intracellular Ca(2+) concentration ([Ca(2+)](i)) in skeletal muscles must be rapidly regulated during the excitation-contraction-relaxation process. However, the signalling components involved in such rapid Ca(2+) movement are not fully understood. Here we report that mice deficient in the newly identified PtdInsP (phosphatidylinositol phosphate) phosphatase MIP/MTMR14 (muscle-specific inositol phosphatase) show muscle weakness and fatigue.

A serious gaming/immersion environment to teach clinical cancer genetics.

We are creating an interactive, simulated "Cancer Genetics Tower" for the self-paced learning of Clinical Cancer Genetics by medical students (go to: http://casemed.case.edu/cancergenetics).

Troponin T core structure and the regulatory NH2-terminal variable region.

The conserved central and COOH-terminal regions of troponin T (TnT) interact with troponin C, troponin I, and tropomyosin to regulate striated muscle contraction. Phylogenic data show that the NH2-terminal region has evolved as an addition to the conserved core structure of TnT. This NH2-terminal region does not bind other thin filament proteins, and its sequence is hypervariable between fiber type and developmental isoforms.

Muscle aging is associated with compromised Ca2+ spark signaling and segregated intracellular Ca2+ release.

Reduced homeostatic capacity for intracellular Ca2+ ([Ca2+]i) movement may underlie the progression of sarcopenia and contractile dysfunction during muscle aging. We report two alterations to Ca2+ homeostasis in skeletal muscle that are associated with aging. Ca2+ sparks, which are the elemental units of Ca2+ release from sarcoplasmic reticulum, are silent under resting conditions in young muscle, yet activate in a dynamic manner upon deformation of membrane structures.

Coupled expression of troponin T and troponin I isoforms in single skeletal muscle fibers correlates with contractility.

Striated muscle contraction is powered by actin-activated myosin ATPase. This process is regulated by Ca(2+) via the troponin complex. Slow- and fast-twitch fibers of vertebrate skeletal muscle express type I and type II myosin, respectively, and these myosin isoenzymes confer different ATPase activities, contractile velocities, and force.

Enhanced resistance to fatigue and altered calcium handling properties of sarcalumenin knockout mice.

Sarcalumenin is a Ca2+-binding protein located in the sarcoplasmic reticulum of striated muscle cells, the physiological function of which has not been fully determined yet. Using sarcalumenin knockout (sar(-/-)) mice, we showed that sar ablation altered store-operated Ca2+ entry (SOCE) and enhanced muscle fatigue resistance. Sar(-/-) mice fatigued less with treadmill exercise, and intact isolated soleus and extensor digitorum longus muscles from sar(-/-) mice were more resistant to intermittent fatiguing stimulation than those from wild-type mice.

Functional and biochemical modifications in skeletal muscles from malarial mice.

Although it is well established that patients suffering from malaria experience skeletal muscle problems (contracture, aches, fatigue, weakness), detailed studies have not been performed to investigate changes in the contractile function and biochemical properties of intact and skinned skeletal muscles of mammals infected with malaria. To this end, we investigated such features in the extensor digitorium longus (EDL, fast-twitch, glyocolytic) and in the soleus (SOL, slow-twitch, oxidative) muscles from mice infected with Plasmodium berghei. We first studied maximal tetanic force (T(max)) produced by intact control and malaria-infected muscles before, during and after fatigue.

Defective maintenance of intracellular Ca2+ homeostasis is linked to increased muscle fatigability in the MG29 null mice.

Mitsugumin 29 (MG29) is a transmembrane protein that is normally found in the triad junction of skeletal muscle. Our previous studies have shown that targeted deletion of mg29 from the skeletal muscle resulted in abnormality of the triad junction structure, and also increased susceptibility to muscle fatigue. To elucidate the basis of these effects, we investigated the properties of Ca2+-uptake and -release in toxin-skinned Extensor Digitorium Longus (EDL) muscle fibers from control and mg29 knockout mice.

Troponin T isoforms alter the tolerance of transgenic mouse cardiac muscle to acidosis.

Troponin T (TnT) is an essential protein in the Ca2+ regulatory system of striated of muscle. Three fiber type-specific TnT genes have evolved in higher vertebrates to encode cardiac, slow and fast skeletal muscle TnT isoforms. To understand the functional significance of TnT isoforms, we studied the effects of acidosis on the contractility of transgenic mouse cardiac muscle that expresses fast skeletal muscle TnT.

Disease prevention and health promotion in medical education: reflections from an academic health center.

Purpose: It is unclear whether academic health centers are successfully addressing societal needs and expectations by preparing students with knowledge and skills in disease prevention and health promotion. The authors assessed whether students were exposed to key content in these areas and whether they felt this exposure was adequate.

Method: All components of the first three years of the Case Western Reserve University (Case) curriculum were examined in 2001 to create a curricular map, using competencies in disease prevention and health promotion identified by the Association of Teachers of Preventive Medicine (ATPM) as a template to assess the scope of instruction.

Truncation by Glu180 nonsense mutation results in complete loss of slow skeletal muscle troponin T in a lethal nemaline myopathy.

A lethal form of nemaline myopathy, named "Amish Nemaline Myopathy" (ANM), is linked to a nonsense mutation at codon Glu180 in the slow skeletal muscle troponin T (TnT) gene. We found that neither the intact nor the truncated slow TnT protein was present in the muscle of patients with ANM. The complete loss of slow TnT is consistent with the observed recessive pattern of inheritance of the disease and indicates a critical role of the COOH-terminal T2 domain in the integration of TnT into myofibrils.

Dysfunction of store-operated calcium channel in muscle cells lacking mg29.

The store-operated calcium channel (SOC) located in the plasma membrane (PM) mediates capacitative entry of extracellular calcium after depletion of intracellular calcium stores in the endoplasmic or sarcoplasmic reticulum (ER/SR). An intimate interaction between the PM and the ER/SR is essential for the operation of this calcium signalling pathway. Mitsugumin 29 (MG29) is a synaptophysin-family-related protein located in the junction between the PM and SR of skeletal muscle.

Influence of ageing on the fatigability of isolated mouse skeletal muscles from mature and aged mice.

We investigated the influence of ageing on the fatiguing characteristics of the mouse extensor digitorum longus (EDL) muscle as compared to those of the soleus muscle. Fatigue was produced by an intermittent stimulation protocol. We report for mature and aged animals the effects of fatigue on force produced during stimulation patterns that in non-fatigued muscle gave maximum force (T(max), high frequency stimulation) and approximately half-maximum force (1/2T(max), low frequency stimulation).